School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, England.
Crit Rev Toxicol. 2011 Oct;41(9):783-802. doi: 10.3109/10408444.2011.598141. Epub 2011 Aug 2.
Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. For a number of endpoints, this requires a detailed knowledge of the electrophilic reaction chemistry that governs the ability of an exogenous chemical to form a covalent adduct. Historically, this chemistry has been defined as compilations of structural alerts without documenting the associated electrophilic chemistry mechanisms. To address this, this article has reviewed the literature defining the structural alerts associated with covalent protein binding and detailed the associated electrophilic reaction chemistry. This information is useful to both toxicologists and regulators when using the chemical category approach to fill data gaps for endpoints involving covalent protein binding. The structural alerts and associated electrophilic reaction chemistry outlined in this review have been incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.
几项法规的出台增加了人们对计算机模拟方法的兴趣，特别是为了评估毒理学终点而形成化学分类。对于许多终点，这需要详细了解亲电反应化学，该化学决定了外源性化学物质形成共价加合物的能力。从历史上看，该化学已被定义为结构警示的汇编，而没有记录相关的亲电化学机制。为了解决这个问题，本文综述了文献中与共价蛋白结合相关的结构警示，并详细介绍了相关的亲电反应化学。当使用化学分类方法填补涉及共价蛋白结合的终点的数据空白时，这些信息对毒理学家和监管机构都很有用。本综述中概述的结构警示和相关亲电反应化学已被纳入经合组织（Q）SAR 工具箱，这是一个免费提供的软件工具，旨在在无需进一步动物测试的情况下填补监管环境中的数据空白。
